D-arginine is an ingredient that is essentially used in the production of medicaments such as desmopressin for the treatment of nocturnal enuresis, icatibant for the treatment of hereditary angioedema, and velcalcetide for the treatment of hyperparathyroidism.
Conventional techniques for preparing D-arginine may be largely classified into two types, one of which is a biological optical resolution reaction process using an enzyme, and the other of which is a chemical optical resolution reaction process using a chiral organic acid.
The preparation of D-arginine through a biological optical resolution reaction includes selectively obtaining D-acetyl-arginine from DL-acetyl-arginine through an optical resolution reaction using an enzyme and then hydrolyzing the D-acetyl-arginine, as is well known [Archives of Biochemistry Biophysics, 39, 108(1952); Archives of Biochemistry Biophysics, 60, 496(1956); The Journal of Biochemistry, 45(9), 687 (1958)], but is problematic because of the large number of processing steps and the requirement for the hydrolysis of D-acetyl-arginine, obtained through an optical resolution reaction, which is the key step, in a hydrochloric acid aqueous solution.
Furthermore, as an additional enzyme-assisted technique, U.S. Pat. No. 5,591,613 discloses a method of preparing D-arginine by selectively converting L-arginine of DL-arginine into L-ornithine using an enzyme, but is problematic because L-arginine contained in DL-arginine is not recovered but is decomposed.
On the other hand, the chemical optical resolution reaction using a chiral organic acid is advantageous in that chemical processing is easily performed using a simple apparatus compared to biological processing, and is thus suitable for mass production, but searching for and selecting chiral organic acids that serve as the optical resolving agent is regarded as very important, but is difficult.
In order to prepare D-arginine from DL-arginine, in Analytical Biochemistry, 63, 68(1975), it was reported that optical resolving agents such as tartaric acid, camphoric acid and glutamic acid have been utilized but failed to obtain desired results, and the separation of D-arginine using L-malic acid was also reported. To this end, however, complicated processing has to be performed in a manner in which a DL-arginine and L-malic acid aqueous solution is crystallized for one day in a refrigerator, thus obtaining primary crystals, which are then concentrated again to give secondary crystals. In particular, only the specific optical rotation ([α]D) of the obtained D-arginine is mentioned, and instrumental analysis by chiral chromatography has not been conducted, undesirably making it impossible to accurately confirm the optical purity of the obtained D-arginine.